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Insulin secretagogues: sulfonylureas They stimulate insulin secretion and are associated with a higher risk of severe hypoglycemia than metformin and other drugs in patients with advanced age and chronic liver or kidney disease.56 They do not modify IR and their effect may be limited in alcoholic individuals due to damage of the beta cells of pancreatic islets.57 Tolbutamide is not recommended in patients with liver disease since half-life increases over 50%.58 Glibenclamide (glyburide) and gliclazide are metabolized in the liver and eliminated through bile and kidney